The research proposed here will investigate the mechanisms of viral persistence and the pathogenesis of lesions in a model system - Aleutian Disease of mink. The overall objectives are to develop in vitro propagation systems and purify and characterize the AD agent. The latter will relate to the virus itself as well as the cell supporting viral replication. The anti-AD immune responses, both humoral and cellular, will be investigated. The influence of AD viral infection on immune responses directed against non-related antigens will be studied. The influence of immunosuppression on the development of the disease utilizing cyclophosphamide and anti-thymocyte serum will also be a part of the research. The pathogenesis of the glomerulonephritis and anemia will be examined in detail. Attempts will also be made to develop resistent strains of mink to study the pathogenesis and mechanisms of viral persistence in resistent mink. In addition, the disease in ferrets will be investigated and compared to the experimental disease in Aleutian and non-Aleutian mink. All of the above will be directed towards the development of an understanding of the mechanisms of viral persistence in AD and the pathogenesis of the lesions.